Morphological changes of macular neovascularization during long-term anti-VEGF-therapy in neovascular age-related macular degeneration

Purpose To analyze the morphological changes of macular neovascularization (MNV) in exudative neovascular age-related macular degeneration under long-term intravitreal anti-vascular endothelial growth factor (VEGF) therapy in a retrospective cohort study. Methods and patients We evaluated 143 nAMD eyes of 94 patients (31 male, 63 female; initial age 55-97 y, mean age 75.9 +/- 7.5 y), who started anti-VEGF therapy (IVAN pro re nata (PRN) protocol) between 2009-2018 and received ongoing therapy until the last recorded visit (mean follow-up 5.3 +/- 2.9 y, range 1-14 y). The mean total number of injections was 33.3 +/- 19.8 with 7.0 +/- 2.3 injections/year. MNV size and, if present, associated complete retinal pigment epithelium (RPE) and outer retina atrophy (cRORA) size were measured on optical coherence tomography (OCT) volume scans at the initial visit and for each year of follow-up. MNV and cRORA were identified on B-scans and their respective borders were manually transposed onto the en-face near infrared image and measured in mm(2). Results MNV enlarged through follow-up, with a mean growth rate of 1.24 mm(2) / year. The mean growth in MNV size was independent of initial MNV size, age, gender, MNV subtypes or number of injections per year. Nevertheless, a great interindividual variation in size and growth was observed. cRORA developed in association with increasing MNV size and its incidence increased linearly over follow-up. cRORA lesions also showed continuous growth by a rate of 1.22 mm(2) / year. Conclusions Despite frequent long-term anti-VEGF therapy, we observed ongoing MNV growth. This is consistent with the concept that the development of MNV may be a physiological biological repair mechanism to preserve RPE and photoreceptor function, provided hyperpermeability and fluid exudation are controlled. Whether recurring low VEGF levels or other factors are responsible for MNV growth remains controversial.